NSAID Safety Differences in Osteoarthritis, Rheumatoid Arthritis Compared
Celecoxib at approved dosages was associated with similar or lower cardiovascular, gastrointestinal, and renal risk for adverse events compared with ibuprofen and naproxen in OA and RA
At approved doses, the use of the nonsteroidal anti-inflammatory drug (NSAID) celecoxib in patients with osteoarthritis (OA) and rheumatoid arthritis (RA) was associated with a similar or a lower risk for cardiovascular (CV), gastrointestinal (GI), and renal adverse events (AEs) compared with ibuprofen and naproxen, according to the results of an international double-blind randomized controlled trial published in Arthritis and Rheumatology.
The investigators of the PRECISION (Prospective Randomized Evaluation of Celecoxib Integrated Safety versus Ibuprofen or Naproxen, ClinicalTrials.gov identifier: NCT00346216) sought to determine the relative CV, GI, and renal safety of celecoxib taken chronically compared with ibuprofen and naproxen in patients with OA and RA.
A total of 24,081 participants with OA (n=21,645) or RA (n=2436) who were at moderate to high CV risk were enrolled in the study. Treatment groups were as follows: In patients with OA, 7259 were treated with celecoxib, 7208 with ibuprofen, and 7178 with naproxen. In patients with RA, 813 were treated with celecoxib, 832 with ibuprofen, and 791 with naproxen.
Doses evaluated were celecoxib 100 to 200 twice daily, ibuprofen 600 to 800 mg 3 times daily, and naproxen 375 to 500 mg twice daily. Main study outcomes included first occurrence of a major adverse cardiac event (MACE), GI events, renal events, and mortality.
Patients in the OA subgroup had a significantly reduced risk for MACE when treated with celecoxib vs ibuprofen (hazard ratio [HR], 0.84; 95% CI, 0.72 to 0.99) but no significantly decreased risk when treated with celecoxib vs naproxen.
In the RA subgroup, the HR for MACE in patients treated with celecoxib vs ibuprofen was 1.06 (95% CI, 0.69 to 1.63) vs 1.22 (95% CI, 0.78 to 1.92) when celecoxib vs naproxen was compared.
Regarding GI events in the OA cohort, the HR was 0.68 (95% CI, 0.51 to 0.91) with celecoxib vs ibuprofen and 0.73 (95% CI, 0.55 to 0.98) with celecoxib vs naproxen. GI events in the RA cohort were as follows: HR of 0.48 (95% CI, 0.22 to 1.07) with celecoxib vs ibuprofen and HR of 0.54 (95% CI, 0.24 to 1.24) with celecoxib vs naproxen.
With respect to risk for renal events, in the OA subgroup, celecoxib vs ibuprofen demonstrated an HR of 0.58 (95% CI, 0.40 to 0.82). Moreover, in the RA subgroup, celecoxib was linked to significantly lower mortality compared with naproxen (HR, 0.47; 95% CI, 0.25 to 0.88).
The investigators concluded that the results of these subgroup analyses of the PRECISION trial confirmed no increased CV risk with celecoxib use. However, celecoxib was associated with slight reductions in the risk for several other outcomes compared with the other commonly used NSAIDs that were evaluated.
These data that demonstrate differential safety across NSAIDs might warrant new recommendations for the optimal use of these agents.
Solomon DH, Husni ME, Wolski KE, et al; PRECISION Trial Investigators. Differences in safety of non-steroidal anti-inflammatory drugs in patients with osteoarthritis and rheumatoid arthritis: a randomized clinical trial [published online December 20, 2017]. Arthritis Rheumatol. doi:10.1002/art.40400